The Mauthner fiber giant fiber synapse of the hatchetfish is a unique preparation for the study of chemical transmission at a vertebrate central synapse. This synapse is specialized for brief periods of rapid activity and its supply of synaptic vesicles can be readily depleted. The objective of the first project is to extend the morphophysiological analysis of transmitter release, fatigue and recovery at an identified synapse. Intracellular injection and extracellular application of agents should lead to progress in our understanding of the processes of packaging, mobilization and release of transmitter. Freeze-fracture and tracer techniques will also be used to further characterize the process of transmitter release as well as that of membrane recycling. The second project is designed to provide information towards understanding the mechanisms of neuronal specificity and the extent of the regulation imposed by differentiating neurons on one another. The amphibian Mauthner cell provides a unique system for the study of neuronal development. For example, with respect to afferent inputs, there is a regional organization of synaptic connections on the cell. Experiments have been designed to see whether this topographic specification is due to regional differences on the surface of the Mauthner cell itself. Other experiments will examine the morphogenesis of the Mauthner cell and its dendrites with respect to interactions with groups of ingrowing axons.